Bentracimab Immediately and Significantly Reverses the Antiplatelet Effects of Ticagrelor in Older People
Reported from ACC 2022
Elad Asher provides his take on this phase IIb trial in healthy people ages 50 to 80 showing that the novel intravenous treatment bentracimab significantly restored platelet function in patients receiving oral P2Y12 inhibitor ticagrelor. The clinical trial was presented by Deepak L. Bhatt at the American College of Cardiology (ACC) 2022 Scientific Session.
Rationale
Ticagrelor is an oral P2Y12 inhibitor that is effective in patients with acute coronary syndromes (ACS), prior myocardial infarction, high-risk coronary artery disease, transient ischemic attack and stroke. As with other antiplatelet drugs, spontaneous major bleeding or bleeding associated with urgent or emergent invasive procedures are concerns.
Although ticagrelor is a reversible P2Y12 inhibitor, the antiplatelet effects of ticagrelor cannot be reversed with platelet transfusion. Therefore, a rapid-acting reversal agent would be useful. Bentracimab is a recombinant human IgG1 monoclonal antibody fragment that binds to free ticagrelor with high affinity and specificity. This allows ADP to active platelets while the bentracimab-ticagrelor complex is eliminated from the bloodstream.
Design
This phase 2B study, was a randomized, double-blind, placebo-controlled (3:1) trial (154 patients received bentracimab while 51 received placebo). 50-80-year-old volunteers pretreated with ticagrelor and aspirin for 48 hours were eligible for the study.
Endpoints
The primary endpoint was % inhibition of PRU within 4 hours by using the VerifyNow. Both the PRU analysis and (the VASP) PRI analysis demonstrated that bentracimab achieved immediate and sustained reversal in 50-80-year-old volunteers who were pretreated with ticagrelor. Moreover, multiple different sub-groups showed similar consistent results in regard to sex, age, race, region (USA/Canada), diabetes mellitus, hypertension and glomerular filtration rate (GRF).
Marker of platelet activation such as P-Selectin and mean platelet volume did not show any evidence of elevated platelet activation post reversal (no “rebound” effect) with bentracimab (or placebo).
Safety profile
There was no significant difference between bentracimab and placebo for any of the treatment adverse events. There were no drug-related serious adverse events and no thrombotic events.
Limitations
Only 50-80-year-old volunteers, no patients with known coronary artery disease, the sample size was modest and, lastly, the study was not designed to evaluate the impact of bentracimab on clinical bleeding events.
Interpretation
The authors concluded that bentracimab significantly restored platelet function as measured by multiple assays, no thrombotic events and no serious adverse events reported in volunteers confirmed the safety profile. Assessment of the drug's clinical effect on patients with bleeding awaits completion of the REVERSE-IT study.
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